Antibodies are natural proteins that the vertebrate immune system forms in response to foreign substances (antigens), primarily for defense against infection. For over a century, antibodies have been induced in animals under artificial conditions and harvested for use in therapy or diagnosis of disease conditions, or for biological research. Each individual antibody producing cell produces a single type of antibody with a chemically defined composition, however, antibodies obtained directly from animal serum in response to antigen inoculation actually comprise an ensemble of non-identical molecules (e.g., polyclonal antibodies) made from an ensemble of individual antibody producing cells.
Some antibody conjugates, such as bispecific antibodies, may bind to two or more different antigens. A number of recombinant strategies have been developed to synthesize bispecific antibodies, which include single chain variable fragment (scFv)-derived formats such as diabodies, tandem diabodies, BiTes (bispecific T-cell engager), and DARTs (Dual Affinity Re-Targeting), as well as immunoglobulin G (IgG)-based formats such as Triomab, DVD-Ig (Dual Variable Domain antibodies), and two-in-one antibodies. However, bispecific antibodies can have poor pharmacokinetics and physical properties, such as immunogenicity and manufacturing challenges. Therefore, there is a need for an improvement or alternative to such existing technology. In addition, precise control over geometry in such a targeting moiety is desirable because the geometry can alter binding affinity and specificity. Disclosed herein are targeting agent antibody conjugates, and methods for producing such conjugates, with specific geometries for optimal therapeutic efficacy and target specificity by the site-specifically coupling of an antibody or antibody fragment to a targeting agent.